There is considerable evidence that CD4+ T-cells play a role in the pathogenesis of rheumatoid arthritis (RA). Certain MHC class II alleles (HLA-DR1 and HLA-DR4, subtypes Dw4, Dw14, and Dw15) are associated with susceptibility to RA. Additional evidence supporting a role for T-cells in RA includes: predominance of Ia+ CD4+ T cells in the synovial mononuclear infiltrates of patients with RA; increased numbers of Ia+ T cells in the peripheral blood of RA patients; evidence of skewed T cell receptor repertoires among infiltrating T cells in the joints of RA patients; improvement of pre-existing RA in patients developing AIDS. Clinical studies have also indicated the T cells as being important in the pathogenesis of rheumatoid arthritis. Thoracic duct drainage, total lymphoid irradiation, and cyclosporine have all been effective in ameliorating chronic refractory rheumatoid arthritis, however, these modalities have been associated with significant side effects. Treatment with murine monoclonal and chimeric monoclonal antibodies to CD4 cells have all shown promise in patients with refractory rheumatoid arthritis. Dr. Larry Moreland as the Priincipal Investigator, has participated in a phase I single center and a phase II multicenter study evaluating this chimeric anti-CD4 MAb in patients with refractory rheumatoid arthritis. Both of these studies were done in the General Clinical Research Center at UAB. The two placebo controlled trials using cM-T412 (early and late disease duration patients) have shown that this MAb was not associated with clinical efficacy. However, an unexpected side effect has been persistent peripheral CD4+ T cell depletion. Our plan is to have these patients treated at UAB (n=50) to return now (approximately 4-5 years after receiving cM-T412) to determine: 1) levels of circulating disease activity by determining the numbers of swollen and painful joints and Westegren erythrocyte sedimentation rate. The long-term follow-up data is valuable to help determine the potential long term effects of MAb therapy for autoimmune disorders.